The emerging role of 27-hydroxycholesterol in cancer development and progression: An update

Saade Abdalkareem Jasim; Hamzah H Kzar; Mohammed Haider Hamad; Irfan Ahmad; Moaed E Al-Gazally; Shukhrat Ziyadullaev; R Sivaraman; Mohammed Abed Jawad; Ali Thaeer Hammid; Khulood H Oudaha; Sajad Karampoor; Rasoul Mirzaei

doi:10.1016/j.intimp.2022.109074

The emerging role of 27-hydroxycholesterol in cancer development and progression: An update

Int Immunopharmacol. 2022 Sep:110:109074. doi: 10.1016/j.intimp.2022.109074. Epub 2022 Jul 21.

Affiliations

¹ Medical Laboratory Techniques Department, Al-maarif University College, Al-anbar-Ramadi, Iraq.
² Veterinary medicine college, Al-Qasim green University, Al-Qasim, Iraq.
³ Medical Laboratory Techniques Department, Al Mustaqbal University college, Babylon, Iraq.
⁴ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.
⁵ College of Medicine, University of Al-Ameed, Karbala, Iraq.
⁶ Professor, Doctor of Medical Sciences, No.1 Department of Internal Diseases, Vice-rector for Scientific Affairs and Innovations, Samarkand State Medical University, Amir Temur Street 18, Samarkand, Uzbekistan.
⁷ Department of Mathematics, Institution of Dwaraka Doss Goverdhan Doss Vaishnav College, Arumbakkam, Chennai, University of Madras, Chennai, India.
⁸ Department of pharmacy, Al-Nisour University College, Baghdad, Iraq.
⁹ Computer Engineering Techniques Department, Faculty of Information Technology, Imam Ja'afar Al-Sadiq University, Baghdad, Iraq.
¹⁰ Pharmaceutical Chemistry Department, College of Pharmacy, Al-Ayen University Thi-Qar, Iraq.
¹¹ Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran. Electronic address: karampour.s@iums.ac.ir.
¹² Venom and Biotherapeutics Molecules Lab, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran. Electronic address: rasul.micro92@gmail.com.

PMID: 35978522
DOI: 10.1016/j.intimp.2022.109074

Abstract

Oxysterols are cholesterol metabolites generated in the liver and other peripheral tissues as a mechanism of removing excess cholesterol. Oxysterols have a wide range of biological functions, including the regulation of sphingolipid metabolism, platelet aggregation, and apoptosis. However, it has been found that metabolites derived from cholesterol play essential functions in cancer development and immunological suppression. In this regard, research indicates that 27-hydroxycholesterol (27-HC) might act as an estrogen, promoting the growth of estrogen receptor (ER) positive breast cancer cells. The capacity of cholesterol to dynamically modulate signaling molecules inside the membrane and particular metabolites serving as signaling molecules are two possible contributory processes. 27-HC is a significant metabolite produced mainly through the CYP27A1 (Cytochrome P450 27A1) enzyme. 27-HC maintains cholesterol balance biologically by promoting cholesterol efflux via the liver X receptor (LXR) and suppressing de novo cholesterol production through the Insulin-induced Genes (INSIGs). It has been demonstrated that 27-HC is able to function as a selective ER regulator. Moreover, enhanced 27-HC production is in favor of the growth of end-stage malignancies in the brain, thyroid organs, and colon, as shown in breast cancer, probably due to pro-survival and pro-inflammatory signaling induced by unbalanced levels of oxysterols. However, the actual role of 27-HC in cancer promotion and progression remains debatable, and many studies are warranted to be performed to unravel the precise function of these molecules. This review article will summarize the latest evidence on the deleterious or beneficial functions of 27-HC in various types of cancer, such as breast cancer, prostate cancer, colon cancer, gastric cancer, ovarian cancer, endometrial cancer, lung cancer, melanoma, glioblastoma, thyroid cancer, adrenocortical cancer, and hepatocellular carcinoma.

Keywords: 27-hydroxycholesterol; CYP27A1; Cancer; Estrogen receptor; Liver X receptor.

Publication types

Review

MeSH terms

Breast Neoplasms* / metabolism
Cholesterol / metabolism
Humans
Hydroxycholesterols
Male
Oxysterols* / metabolism

Substances

Hydroxycholesterols
Oxysterols
27-hydroxycholesterol
Cholesterol